TRAIL-death receptor endocytosis and apoptosis are selectively regulated by dynamin-1 activation | PNAS thumbnail
TRAIL-death receptor endocytosis and apoptosis are selectively regulated by dynamin-1 activation | PNAS
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TRAIL–DR-mediated ryanodine receptor activation and endocytosis is dependent on early caspase-8 activation. Dynamins are master regulators of CME Binding of human recombinant TRAIL to its cognate apoptosis-inducing DR (DR4 or DR5) stimulates their internalization via CME Taken together, our findings
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  • TRAIL–DR-mediated ryanodine receptor activation and endocytosis is dependent on early caspase-8 activation.
  • Dynamins are master regulators of CME
  • Binding of human recombinant TRAIL to its cognate apoptosis-inducing DR (DR4 or DR5) stimulates their internalization via CME
  • Taken together, our findings confirm previous reports (21, 22) of an important role for TRAIL–DR endocytosis in the negative regulation of TRAIL-induced apoptosis, and furthermore, establish the existence of cargo-selective, dynamin isoform-specific mechanisms for endocytosis.
  • Dyn1 can also be activated through dephosphorylation by the calcium (Ca2+) and calmodulin-dependent phosphatase, calcineurin (29, 30). Inhibiting calcineurin by either cyclosporin A (CsA) (Fig. 2B) or FK506 (Fig. S4), resulted in a significant increase in sensitivity to TRAIL-induced apoptosis in A549 WT cells, comparable to the levels seen in Dyn1...

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